In view of the predominant role played by antibodies to nucleic acid antigens in the pathogenesis of lupus nephritis, we are attempting to induce tolerance to DNA to control manifestation of the disease. We have shown that the combination of cortisone and tolerogen appears to be the best therapy for increasing survival. Cytoxan, although it increases survival by itself, does not facilitate tolerance to nucleoside. We have also found that female BWF1 mice seem to break tolerance to endogenous nucleic acid antigens more rapidly than do males. Consistent with this observaton, strain and sex differences were also found in tolerance to exogenous nucleic acid antigens. We are currently working on two new areas: 1) We have extended the concept of using cell bound antigens as tolerogen to the treatment of murine lupus nephritis, and have been successful in raising suppressor T cells specific for nucleoside. The demonstration of nucleic acid specific suppressor T cell now permits us to examine whether or not they play any role in the pathogenesis of systemic lupus. 2) A new tolerogen made up of oligonucleotide-IgG has been syntesized. The immunogenicity and tolerogenicity of this new compound is being tested in vivo.